Field of the Invention
The present invention relates to the field of metabolic engineering, and more particularly relates to a method for weakening pyruvate catabolism and improving the accumulation of pyruvate in microbes.
Description of the Related Art
Pyruvate (Pyruvic acid) is one of the important intermediates in the tricarboxylic acid cycle (TCA cycle). It not only plays a key role in microbial metabolisms, such as energy metabolism and synthesis of amino acids, proteins and vitamins, but also occupies the key regulation point of TCA cycle. Compared with the other intermediates in the TCA cycle, regulations for pyruvate metabolism are much more complicated.
As an essential intermediate in fine chemicals and pharmaceutical industry, pyruvic acid is widely used in the synthesis of amino acids, vitamins and other organic molecules. It also has a wide range of applications in pharmaceutics, organic synthesis and nutritional supplement synthesis. In order to meet the rising market demand, more effective methods for synthesizing pyruvic acid are needed.
There are many problems, such as poor efficiency and low yield, when producing pyruvic acid using microbes. Genetic modification is necessary for high level productivity. However, to those obligated aerobes, pyruvic acid is at the key position of the energy supply chain. It may cause side effects to cell growth even death if genes of the central metabolic pathway are knocked out. Particularly, pyruvate producing yeast cells belong to obligate aerobic microorganism, and genomic deletion of key enzymes in TCA cycle pathways could be lethal. The present invention provides a method to decrease the catabolism of pyruvate and thus increase the accumulation of pyruvate in microbes while avoiding lethal effects caused by modification of key TCA components in the engineered microbes.